The present invention generally relates to electrochemical sensors and, in particular, to molded electrochemical sensors for detection or measurement of analytes in test samples, such as fluids and dissolved solid materials, and the methods of making and using these sensors.
Electrochemical sensors are used to determine the concentrations of various analytes in testing samples such as fluids and dissolved solid materials. For instance, electrochemical sensors have been made for measuring glucose in human blood. Such sensors have been used by diabetics and health care professionals for monitoring blood glucose levels. The sensors are usually used in conjunction with a meter, which measures light reflectance, if the strip is designed for photometric detection of a die, or which measures some electrical property, such as electrical current, if the strip is designed for detection of an electroactive compound.
Typically, electrochemical sensors are manufactured using an electrically insulating base upon which conductive inks such as carbon and silver are printed by screen printing to form conductive electrode tracks or thin strips of metal are unrolled to form the conductive electrode tracks. The electrodes are the sensing elements of the sensor generally referred to as a transducer. The electrodes are covered with a reagent layer comprising a hydrophilic polymer in combination with an oxidoreductase or a dehydrogenase enzyme specific for the analyte. Further, mounted over a portion of the base and the electrodes is an insulating layer.
Precision and accuracy of electrochemical measurements to a great extent rely on the reproducibility of the electrode surface area on a microscopic scale. Variations in the morphology of the electrode can result in very significant changes in the electrochemical signal readout. Screen-printing has made significant in-roads in the production of sensors for determining glucose. The wide use of screen-printing stems from the ability to mass-produce relatively inexpensive sensors. The use of metal strips unrolled from large rolls has also been employed to mass produce such sensors.
While many advances have been made in the field of screen printing and conductive ink production, the technology still suffers from poor reproducibility of the electrode surface area, dimensional variations, thickness variations, micro-cracks, and shrinkage due to the repetitive and high temperature curing processes involved in using film printing technology. Loss of solvent during printing is another factor that leads to variations in the thickness of electrodes.
Sensor development using printing technology requires several passes of different conductive inks demanding different screens. Slight variations in positioning the screens can lead to substantial errors in IR drop and the applied potentials. Wear and tear of these screens is another source of error. Also, sensor strip production by screen printing suffers from a high level of raw material waste. Generally, for every gram of ink used, there is a gram of ink wasted. Manufacture of such sensors also involves several lamination processes that add to the production complexity and cost of the final product.
The present invention is an electrochemical sensor that provides for the determination of various analyte concentrations in a testing sample such as fluids and dissolved solid materials. The sensor is designed to facilitate production in large quantities using reliable and cost effective injection molding manufacturing methods. The present invention includes an injection molded plastic strip or body, at least two electrodes, an enzyme, and if desired, an electron transfer mediator. The body includes a cavity or reaction zone for receiving a fluid sample. The electrodes are at least partially embedded within the plastic body and extend into the reaction zone where they are exposed to a test sample. Also contained within the reaction zone is an enzyme capable of catalyzing a reaction involving a compound within the fluid sample.
Specifically, the device cooperates with an electronic meter capable of measuring the difference between the electrical properties of the electrically conductive electrodes within the device. The device, a sensor, includes at least two, and preferably three, spaced apart electrically conductive electrodes, a body having two ends of insulative material molded about and housing the electrodes, means for connecting the meter to the housing, means for receiving a fluid sample, and means for treating one or more electrodes with one or more chemicals to change the electrical properties of the treated electrodes upon contact with the fluid sample. One end of the housing has the means for connecting the meter and the opposite end of the housing has the means for receiving the fluid sample. The means for connecting the meter is a plug formed in the housing exposing the electrodes outside the body.
The sensor is molded and can be a single, unitary piece or two pieces. In the two piece construction, an end cap is attached to the body. In the single piece construction, the body pivots about a hinge and connects onto itself. Protuberances formed in a portion of the body cooperate with troughs to ensure proper alignment.
A capillary inlet is constructed at one end of the sensor to draw the fluid sample into the body upon contact with the fluid sample. The capillary inlet is molded into the end of the body and is in communications with a reaction zone. This reaction zone is a channel formed in the body about the electrodes and is adapted for reacting with the fluid drawn into the body by the capillary force. While the reaction zone may be formed above or below the electrodes, the preference has been to construct it above the electrodes. The capillary has a vent for relieving pressure.
As noted, the electrodes are molded into the plastic. In one embodiment, the electrodes are conductive wires. In another embodiment, the electrodes are constructed from a metal plate. The electrodes may be coated with a different conductive material to enhance their performance.
Apertures are formed in the body of the sensor to permit the holding of the electrodes during the molding process. Apertures may also be formed in the body to chemically treat one or more electrodes in the reaction zone before or after the molding process. Adding chemicals (e.g., reagents with and without enzymes) changes the electrical properties of the treated electrodes upon contact with the fluid sample. In the preferred embodiment, the enzyme is applied to the outer surface of one of the electrodes. An antibody may also be applied to another of the electrodes. An electron mediator may further be applied to the outer surface of one or more of the electrodes.
In another embodiment in accordance with the invention, the sensor provides fill detection. Fluid drawn into the capillary inlet and the reaction zone contacts the edges of the electrodes, and upon reaching the lower end of the reaction zone, the area farthest from the capillary inlet, activates the meter. When the fluid comes in contact with the last electrode in the capillary space, it closes an open circuit in the electrochemical cell causing current to flow through the cell. The flow of current in the cell triggers the meter, signaling that the capillary chamber is filled with fluid. The vent could also be used for a visual detection of fluid fill.
The methods of making and using the electrochemical sensor are also disclosed. The method of making the device includes the steps of positioning at least two spaced apart electrically conductive electrodes in a mold, before or after molding treating at least one of the electrodes with one or more chemicals to change the electrical properties of the treated electrode upon contact with a fluid sample, and molding a body of insulative material with two ends around the electrodes with one end having therein means for receiving a fluid sample. As before, the body is molded in two pieces, with a body and end cap for attaching to one another after the molding is completed, or in a single, unitary piece.